This application claims priority under 35 U.S.C. xc2xa7119 of commonly owned PCT Application No. PCT/GB98/03884, filed Dec. 23, 1998. This application designated the United States and was published in the English language on Jul. 08, 1999 as WO 99/33832. The PCT application claims priority from British Patent Application No. GB 9727301.5, filed Dec. 23, 1997.
The present invention relates to new cytotoxic alkaloids, Asmarine A and B, isolated from the sponge Raspailia sp.
Marine organisms, especially soft corals, sponges and tunicates, provide many secondary metabolites and exhibit a varying degree of biological activity (Reference 1). A family of these metabolites is the diterpene-alkaloid family; in 1984 (Reference 2) it was reported the structure of four Agelasines: 
We have isolated from the sponge Raspailia sp. new cytotoxic diterpene-alkaloids related to this agelasine family.
The present invention provides new diterpene-alkaloid having either the formula (I) or the formula (II): 
wherein R1 represents hydrogen or lower alkyl or lower alkanoyl; R2 represents hydrogen or lower alkyl; R3 is either an alkyl or a cycloalkyl group containig one or more isoprene units, or a monoterpene or a sesquiterpene or a diterpene group; R4 and R5 represent hydrogen or lower alkyl; R6 represents lower alkyl; X represents F or Cl or Br or I.
In the definitions of the groups in formulas (I) and (II), the lower alkyl and the lower alkyl moiety of the lower alkanoyl mean a straight-chain or branched alkyl group having 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, neopentyl and hexyl.